rs9061

Variant names:

• chr2-230212395-C-T
• rs9061
• NM_080424.4:c.619G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_080424.4(SP110):​c.619G>A​(p.Glu207Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,612,608 control chromosomes in the GnomAD database, including 9,687 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (742 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8945 hom.)
• Consequence: SP110 NM_080424.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.444
• Publications: 32 publications found

Genes affected

SP110 (HGNC:5401): (SP110 nuclear body protein) The nuclear body is a multiprotein complex that may have a role in the regulation of gene transcription. This gene is a member of the SP100/SP140 family of nuclear body proteins and encodes a leukocyte-specific nuclear body component. The protein can function as an activator of gene transcription and may serve as a nuclear hormone receptor coactivator. In addition, it has been suggested that the protein may play a role in ribosome biogenesis and in the induction of myeloid cell differentiation. Alternative splicing has been observed for this gene and three transcript variants, encoding distinct isoforms, have been identified. [provided by RefSeq, Jul 2008]

SP140 (HGNC:17133): (SP140 nuclear body protein) This gene encodes a member of the SP100 family of proteins, which are share common domains including an N-terminal homogeneously staining region domain followed by a SP100/autoimmune regulator/NucP41/P75/deformed epidermal autoregulatory factor domain, a plant homeobox zinc finger, and a bromodomain. The encoded protein is interferon-inducible and is expressed at high levels in the nuclei of leukocytes. Variants of this gene have been associated with multiple sclerosis, Crohn's disease, and chronic lymphocytic leukemia. Alternative splicing results in multiple variants. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0052110553).
• BP6: Variant 2-230212395-C-T is Benign according to our data. Variant chr2-230212395-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 334910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080424.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	NM_080424.4	MANE Select	c.619G>A	p.Glu207Lys	missense	Exon 5 of 19	NP_536349.3	Q9HB58-6
	SP110	NM_001378442.1		c.637G>A	p.Glu213Lys	missense	Exon 6 of 20	NP_001365371.1
	SP110	NM_001378443.1		c.619G>A	p.Glu207Lys	missense	Exon 5 of 19	NP_001365372.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	ENST00000258381.11	TSL:2 MANE Select	c.619G>A	p.Glu207Lys	missense	Exon 5 of 19	ENSP00000258381.6	Q9HB58-6
	SP110	ENST00000358662.9	TSL:1	c.619G>A	p.Glu207Lys	missense	Exon 5 of 18	ENSP00000351488.4	Q9HB58-1
	SP110	ENST00000258382.10	TSL:1	c.619G>A	p.Glu207Lys	missense	Exon 5 of 15	ENSP00000258382.5	Q9HB58-3

Frequencies

GnomAD3 genomes AF: 0.0936 AC: 14243 AN: 152122 Hom.: 741 Cov.: 32

Gnomad AFR AF: 0.0757

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.0654

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.0596

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0966

Gnomad OTH AF: 0.0975

GnomAD2 exomes AF: 0.111 AC: 27759 AN: 251134 AF XY: 0.118

Gnomad AFR exome AF: 0.0756

Gnomad AMR exome AF: 0.0432

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.178

Gnomad FIN exome AF: 0.0580

Gnomad NFE exome AF: 0.0966

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.101 AC: 147593 AN: 1460368 Hom.: 8945 Cov.: 31 AF XY: 0.106 AC XY: 77078 AN XY: 726556

African (AFR) AF: 0.0808 AC: 2702 AN: 33448

American (AMR) AF: 0.0475 AC: 2123 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 4224 AN: 26126

East Asian (EAS) AF: 0.173 AC: 6846 AN: 39668

South Asian (SAS) AF: 0.231 AC: 19870 AN: 86204

European-Finnish (FIN) AF: 0.0597 AC: 3190 AN: 53416

Middle Eastern (MID) AF: 0.169 AC: 975 AN: 5766

European-Non Finnish (NFE) AF: 0.0909 AC: 100989 AN: 1110660

Other (OTH) AF: 0.111 AC: 6674 AN: 60358

GnomAD4 genome AF: 0.0936 AC: 14257 AN: 152240 Hom.: 742 Cov.: 32 AF XY: 0.0945 AC XY: 7038 AN XY: 74442

African (AFR) AF: 0.0762 AC: 3164 AN: 41538

American (AMR) AF: 0.0653 AC: 999 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 554 AN: 3472

East Asian (EAS) AF: 0.168 AC: 873 AN: 5186

South Asian (SAS) AF: 0.237 AC: 1141 AN: 4824

European-Finnish (FIN) AF: 0.0596 AC: 632 AN: 10606

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.0966 AC: 6569 AN: 68002

Other (OTH) AF: 0.0970 AC: 205 AN: 2114

Alfa AF: 0.0985 Hom.: 620

Bravo AF: 0.0899

TwinsUK AF: 0.0930 AC: 345

ALSPAC AF: 0.0851 AC: 328

ESP6500AA AF: 0.0776 AC: 342

ESP6500EA AF: 0.0938 AC: 807

ExAC AF: 0.114 AC: 13871

Asia WGS AF: 0.168 AC: 584 AN: 3478

EpiCase AF: 0.0975

EpiControl AF: 0.0985

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Hepatic veno-occlusive disease-immunodeficiency syndrome (3)
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.2
DANN	Benign	0.60
DEOGEN2	Benign	0.0014	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.44
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.053
Sift	Benign	0.20	T
Sift4G	Benign	0.34	T
Polyphen		0.049	B
Vest4		0.16
MPC		0.34
ClinPred		0.010	T
GERP RS		-4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.026
gMVP		0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9061; hg19: chr2-231077110; COSMIC: COSV51246462; COSMIC: COSV51246462;